Regional Anesthesia for Sickle Cell Disease Vaso-occlusive Crisis: A Single-Center Case Series

Abstract

Pain management is challenging for patients with sickle cell disease (SCD) who present in vaso-occlusive crisis (VOC). Opioid therapy is highly effective, nevertheless undesirable side effects can hinder their effectiveness.

Regional anesthesia with deposition of perineural anesthetic offers nociceptive blockade, local vasodilatation and reduces the inflammatory response. Among pediatric patients, continuous peripheral nerve block (CPNB) for perioperative adjunctive analgesia is safe. Herein, we describe the trajectory of a cohort of pediatric SCD patients with opioid-refractory upper extremity VOC following placement of CPNBs for analgesia; highlighting reduced opioid consumption, improved pain scores and decreased length of hospitalization.

Introduction

Sickle cell disease (SCD) comprises a group of hemoglobinopathies hallmarked by chronic hemolysis and recurrent vaso-occlusive crises (VOC), resulting in multi-organ dysfunction and early mortality. Disease-modifying therapies, such as hydroxyurea, have been shown to decrease VOC frequency. Admittedly, acute pain management remains particularly challenging.[1,2]

Opioids are a well-established therapy for VOC pain. However, the opioid-related side effects of sedation and respiratory depression can precipitate hypoxemia and atelectasis, worsening the underlying SCD pathophysiology. To minimize these risks, adjunctive therapies have been deployed, including: lidocaine, non-steroidal anti-inflammatories and muscle relaxants.[3–8]

Peripheral and central nerve blockade provides optimal analgesia for acute and chronic pain. Within the pediatric population, regional anesthesia (RA) utilizing continuous peripheral nerve block (CPNB) is safe and efficacious for perioperative and acute pain management.[9] Thoracic epidural analgesia has been successfully used for SCD-related pain management in acute chest syndrome.[10,11] However, the use of CPNB for extremity VOCs in this patient population has only been described in a few case reports.[12,13] This is the first case series to highlight uniform CPNB pain management for three patients with upper extremity VOCs.

Case Description

Case 1

A 16-year-old with HbSS was admitted for severe bilateral upper extremity VOC. Her right arm pain resolved within 48-hours, albeit sedation with oxygen requirement, pruritus and constipation ensued. On hospital day-3, she developed sharp pain radiating from the left shoulder to the elbow. This pain was exacerbated with motion and unresponsive to opioid titration; sub-anesthetic ketamine was initiated. Diagnostic radiography demonstrated avascular necrosis (AVN) of the left humeral head. Deep venous thrombosis was ruled out. The RA pain service was consulted on day-5 and offered a supraclavicular CPNB. With minimal sedation (ketamine 60mg, midazolam 2mg) under direct visualization with a high-frequency linear ultrasound transducer, a 22-G-echogenic needle was inserted in-plane postero-lateral to the subclavian artery. Ropivacaine (40mg) was deposited perineurally to the brachial plexus, followed by placement of a CPNB catheter. The CPNB was maintained for two days with a ropivacaine infusion (0.1mg/kg/hr). She was successfully weaned to an oral opioid regimen within 12-hours post-block and required no opioids by 24-hours. Ketamine infusion was discontinued on day-6. She was discharged on day-7. There was no evidence of CPNB complication. Post-hospitalization clinic follow-up at twelve days was notable for sustained pain resolution with limited oral opioid breakthrough requirement.

Case 2

A 13-year-old with HbSS and humeral AVN was admitted with back and shoulder VOC. His left shoulder pain persisted despite opioid titration. Moreover, he developed opioid-induced constipation and sedation with supplemental oxygen requirement. On hospital day-7, the RA service performed an interscalene CPNB under minimal sedation (ketamine 60mg, midazolam 2mg), as previously described. Ropivacaine (16mg) with dexmedetomidine (4mcg) was deposited perineurally. Thereafter, a ropivacaine infusion was initiated (0.1mg/kg/hr). He was weaned to an oral opioid regimen over the ensuing 16-hours and required no opioids 24-hours post-CPNB. The catheter was discontinued without complication following two days of treatment. He was discharged on day-10 and did not return for post-hospitalization outpatient clinic follow-up.

Case 3

An 11-year-old with HbS/β−0-thalassemia presented with severe neck, back and bilateral upper extremity VOC. Sub-anesthetic ketamine was initiated on hospital day-1. His pain improved however, he developed ketamine-associated hallucinations. Ketamine was discontinued on day-5 and he transitioned to oral opioids. On day-7, his right upper extremity acutely worsened requiring reinstitution of parental opioids. Imaging demonstrated AVN of the right humeral head. Under minimal sedation (ketamine 70mg, midazolam 2mg, dexmedetomidine 12mcg), the RA pain service placed an interscalene CPNB on day-10. Following a bolus dose of ropivacaine (50mg), he was maintained on a ropivacaine infusion (0.1mg/kg/hr). Parenteral and oral opioids were discontinued within 16-hours of CPNB placement. The CPNB was maintained for 48-hours and removed without complication. He was discharged on day-12. Post-hospitalization clinic follow-up at 1 week was notable for sustained pain resolution without home opioid requirement.

Methods

In this retrospective case series, we investigated patients hospitalized with VOC at Texas Children’s Hospital between September-December 2020. Informed consent was obtained from the parent(s) for this scientific contribution.

Results

All patients underwent CPNB placement for persistent localized pain despite multimodal therapy (Table 1). Pain scores and opioid consumption decreased within 24 hours of CPNB placement (Figure 1). Opioid reduction within the first 24 hours post-block ranged from 47.5% to 79.6%. Similarly, numeric pain scores decreased from 7–9/10 pre-block to 0–1/10 post-block. All patients were discharged within 48 hours of initiation of CPNB treatment.

Table 1:

Patient demographics and clinical course

	Indication	Block and Catheter	%Change in opioid use#	Catheter duration	Opioid related adverse events	Multimodal adjuncts for pain management	Admission duration
Case 1 16y F with HbSS (wt: 60kg)	Left upper extremity pain (AVN of left humeral head)	Left Supraclavicular nerve block catheter	−78.7%	2 days	Constipation Sedation pruritis	Ketorolac Ketamine Acetaminophen Lidocaine patch	6 days
Case 2 13y M with HbSS (wt: 59kg)	Left shoulder pain (history of AVN)	Left interscalene nerve block catheter	−47.5%	2 days	Constipation Sedation	Ketorolac/Ibuprofen Acetaminophen Lidocaine patch Methocarbamol	10 days
Case 3 11y M with HbS/β0 (wt: 59kg)	Right upper extremity pain (AVN of right humeral head)	Right interscalene nerve block catheter	−79.6%	2 days	Constipation	Ketorolac/Ibuprofen Ketamine Acetaminophen Lidocaine Patch Methocarbamol Gabapentin Diclofenac gel	12 days

AVN = avascular necrosis.

^#percent change in opioid use, comparing 24 hours prior to block and 24 hours after block. (%change)= [(pre-block use)-(post-block use)]/(pre-block use)*100%

FIGURE 1. Hospital Opioid Consumption pre-CPNB and post-CPNB.

Day 0 is considered the day of CPNB. The black line represents CPNB. Shaded areas (Blue- case 1, Purple- case 2, Green- case 3) represent daily opioid consumption in morphine equivalents, mg/kg. Orange dots represent patient reported pain scores at 8am, 12pm, 4pm and 8pm. CPNB = Continuous peripheral nerve block.

Discussion

Acute VOC pain is the leading cause of hospital utilization for patients with SCD.[14] Pain management is challenging due to limited treatment modalities.[15,16] Pharmacotherapy for VOC targets peripheral and central nociceptive and inflammatory-mediated pathways. Opioid therapies are judicious, as they potently inhibit central and peripheral µ-receptors but they carry numerous undesirable side effects, most notably sedation, respiratory depression, increased risk of acute chest syndrome (ACS), constipation and opioid-induced hyperalgesia.[17,18] Incorporating RA proved instrumental in our subset of patients with VOC and humeral head AVN, resulting in decreased opioid requirement, markedly improved pain, and reduced length of hospitalization.

Among surgical patients, RA blunts autonomic nociception and the inflammatory response when compared to opioids, thereby reducing C-reactive protein and leukocyte counts.[6,19–20] Additionally, RA promotes vasodilation to improve local tissue oxygenation, which has been demonstrated in a prospective analysis using near-infrared spectroscopy.[21]

Retrospective case reports have shown beneficial outcomes with reduced opioid requirement, decreased length of hospitalization and improved patient satisfaction for RA in isolated limb VOC.[12,13] While there are no randomized clinical trials investigating the longitudinal efficacy and safety of RA in VOC, the available data suggests a role for RA exists. The 2020 American Society of Hematology (ASH) guidelines for management of acute and chronic pain in SCD provided recommendations for interdisciplinary and multimodal approaches for the treatment of pain.[22] With this goal in mind, ASH highlights RA for both adults and children presenting with acute, focal opioid-refractory SCD pain.

As with all clinical decision-making, an individualized approach is required when considering the addition of RA to the VOC pain regimen. Children and adolescents with isolated limb VOC are ideal candidates for RA. Appropriately dosed local anesthetics that facilitate sensory blockade with preservation of motor function and physical activity through an indwelling nerve block catheter or single injection can significantly reduce opioid consumption and support patient rehabilitation, as in our cohort. Procedural related risks including infection, hematoma and neurological injury such as peripheral neuropathy exist; albeit the reported incidence is extremely low.[23,24] General anesthesia increases the risk of SCD-related complications such as hypoxia, atelectasis, hypercarbia, acidosis and worsening VOC. However, ultrasound guidance and local anesthetics allow for CPNB to be performed with monitored anesthesia care or mild sedation, thereby reducing the risks associated with general anesthesia.[25] Procedural sedation with dexmedetomidine and sub-anesthetic ketamine preserves respiratory function and airway reflexes, mitigating the deleterious effects of general anesthesia. Collaborative pre-operative assessment is important, particularly for patients requiring sedation, and may require preparation with pre-procedure blood transfusion.[26]

Among our subset of pediatric patients, CPNB for limb VOC achieved dramatic reductions in pain scores and opioid utilization following 24-hours of therapy, and hospital discharge within 48-hours. While it remains unknown if RA addresses the underlying pathophysiology of VOC, our continued patient benefit at 1–2 week follow-up was promising. Future investigations examining the mechanisms of RA in VOC, the utility of RA as a primary modality for VOC and AVN-mediated pain, and the long-term safety and efficacy outcomes are warranted.

Key Points:

• Regional anesthesia is an adjunct for pain management in sickle cell disease patients with localized vaso-occlusive crisis (VOC)

• A hematology and regional anesthesiology collaborative can streamline VOC patients who will benefit most from peripheral nerve blocks

Abbreviations

ACS

acute chest syndrome

ASH

American Society of Hematology

AVN

avascular necrosis

CPNB

continuous peripheral nerve block

NMDA

N-methyl-D-aspartate

RA

regional anesthesia

SCD

sickle cell disease

VOC

vaso-occlusive crisis